Copy number variants in a sample of patients with psychotic disorders: is standard screening relevant for actual clinical practice?

Abstract

Noortje WA Van de Kerkhof,1 Ilse Feenstra,2 Jos IM Egger,1,3,4 Nicole de Leeuw,2 Rolph Pfundt,2 Gerald Stöber,5 Frank MMA van der Heijden,1 Willem MA Verhoeven1,61Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands; 2Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands; 3Donders Institute for Brain, Cognition and Behaviour, 4Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands; 5University of Würzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Würzburg, Germany; 6Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, The NetherlandsAbstract: With the introduction of new genetic techniques such as genome-wide array comparative genomic hybridization, studies on the putative genetic etiology of schizophrenia have focused on the detection of copy number variants (CNVs), ie, microdeletions and/or microduplications, that are estimated to be present in up to 3% of patients with schizophrenia. In this study, out of a sample of 100 patients with psychotic disorders, 80 were investigated by array for the presence of CNVs. The assessment of the severity of psychiatric symptoms was performed using standardized instruments and ICD-10 was applied for diagnostic classification. In three patients, a submicroscopic CNV was demonstrated, one with a loss in 1q21.1 and two with a gain in 1p13.3 and 7q11.2, respectively. The association between these or other CNVs and schizophrenia or schizophrenia-like psychoses and their clinical implications still remain equivocal. While the CNV affected genes may enhance the vulnerability for psychiatric disorders via effects on neuronal architecture, these insights have not resulted in major changes in clinical practice as yet. Therefore, genome-wide array analysis should presently be restricted to those patients in whom psychotic symptoms are paired with other signs, particularly dysmorphisms and intellectual impairment.Keywords: schizophrenia, psychotic disorders, microarray, copy number variants, 1q21, 7q11.2, 1p13.3